FFAR2
protein-codingfree fatty acid receptor 2, the group of Free fatty acid receptors
Gene summary
This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]
Previous symbols:
- GPR43
MANE transcript
NM_001370087.1
Inheritance
—
ClinVar variants
U:75B:4
Top phenotype
—
gnomAD constraint
pLI —, LoF o/e 0.55
Max pathogenic AF
—
Genomic locus
chr19:35,443,907-35,451,767
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.9 kbLoading mutation effect viewer...
GenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FFAR2 variants in ClinVar
not specifiedTotal: 77
not providedTotal: 2
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001370087.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 75 | 2 | 1 | 78 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 75 | 2 | 2 | 79 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 7 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001357016.1 | 1 | MANE Select | |
| Ensembl | ENSP00000473159.1 | 1 | MANE Select | |
| RefSeq | NP_005297.1 | 1 | Standard | |
| Ensembl | ENSP00000246549.2 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- cAMP signaling pathway - Homo sapiens (human)
- SCFA and skeletal muscle substrate metabolism
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
Biological Process
- leukocyte chemotaxis involved in inflammatory response
- mucosal immune response
- regulation of acute inflammatory response
- positive regulation of cytokine production involved in immune response
- cell surface pattern recognition receptor signaling pathway
Molecular Function
- G protein-coupled receptor activity
- protein binding
- lipid binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000599180
- Coding exons
- 1
- Length
- 7861
- Individuals with no LoFs
- 125679
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125747
- p
- 0.000270
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.122 | 205 | 210 | 0.976 | 0.0000140 | 2105 |
| Missense (PolyPhen) | 75 | 83.992 | 0.89295 | 911 | ||
| Synonymous | 0.447 | 90 | 95.6 | 0.942 | 0.00000631 | 740 |
| Loss of Function | 1.11 | 4 | 7.22 | 0.554 | 3.97e-7 | 64 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:12496283, PubMed:12711604, PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine. May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake. Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes. In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines. May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils. In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin- 8/IL-8 in response to the presence of microbes (PubMed:21037097). Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably acetate, propionate and butyrate (PubMed:12496283, PubMed:12711604). Exhibits a SCFA- independent constitutive G protein-coupled receptor activity (PubMed:23066016). {ECO:0000269|PubMed:12496283, ECO:0000269|PubMed:12684041, ECO:0000269|PubMed:12711604, ECO:0000269|PubMed:18801738, ECO:0000269|PubMed:21037097, ECO:0000269|PubMed:23066016, ECO:0000269|PubMed:23589301}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.506
- RVIS EVS
- 0.46
- RVIS percentile EVS
- 78.59
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.262
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |